[Consent in children: Practical situations (part 2)]. / Recherche en pédiatrie (2) : le consentement en pratique.

Ethical and regulatory documents frame informed consent in pediatric research; their application is obligatory but may be complex. In this specific context, pediatric investigators have a central ethical role to play to ensure the strict respect of regulatory and ethical requirements adapted to the French legal, social, and cultural context as well as good clinical practices. This article attempts to shed light on the considerations that can allow researchers to come to terms with industrial and institutional demands while responding to the needs of patients, particularly in the domain of pediatric research.

[Legal aspects of consent in children (Part 1)]. / Recherche en pédiatrie (1) : dispositions juridiques relatives au consentement.

In pediatric research, the patient is legally a minor and therefore protected by law. Research can only be conducted after parental consent and patient assent have been obtained. In this context, this review discusses the historical events and documents related to all ethical precautions and obligations. It also underlines that physicians shall respect all legal measures, but that individual involvement must comply with ethical standards while taking into account issues particular to pediatric research related to parental consent and child assent to clinical trials.

[Good clinical practice in clinical trials: training clinicians,incentives to apply good clinical practice and assessment of compliance]. / Bonnes Pratiques des essais Cliniques: formation des médecins, incitations à la mise en oeuvre des B.P.C. et évaluation de leur observance.

Fourteen years after the concept was created, it seemed important to assess how well investigators actually apply Good Clinical Practice. Various sources of information have revealed a general deficiency in their application: "investigation by the working group, Afssaps (French Agency for the Safety of Health-Care Products) inspections, industrial data". The deficiencies identified stem from different factors: lack of professionalization, lack of training, lack of motivation, the large numbers of poorly conducted studies. The working group drew up proposals intended to improve the training of investigators, to dissuade investigators from pursuing inadequate procedure and to verify the level of compliance. However in this respect, the investigator is not the only one at fault. Improved practice unavoidably requires better assistance on the part of the sponsors, more consistent supervision of monitoring, and greater vigilence by the authorities involved in the control and use of trials.

[ Legal aspects of advice provided by an institutional pharmacovigilance specialist to health-care professionals. Consequences in the field of teratology ]. / Aspects juridiques des conseils donnés par un pharmacovigilant institutionnel aux professionnels de santé. Conséquences dans le champ de la tératologie.

An institutional pharmacovigilance specialist gives advice only when consulted by a prescribing physician about a pregnant woman. The situation may involve a pregnant woman for whom a prescription may be considered or a pregnant woman for whom a prescription has been given. The aim is to evaluate the risk for the fetus, both before and after the fact. In view of recent decisions by the Cour de Cassation (*) which imposed penalties for preventing a woman exposed to a teratogenic risk from resorting to an abortion by providing her with inapropriate information, we are suggesting here the hypothesis that an institutional pharmacovigilance specialist acting as a consultant could be implicated. However, this hypothesis is purely academic. If action were taken to render a pharmacovigilance specialist liable, it is in fact the State that would have to answer.

[Women in clinical trials]. / Les femmes dans les essais cliniques.

In a workshop held in Giens in September 1994, representatives of drug companies and scientists met to discuss the place of women in clinical trials. They recommend that, in phase II and III studies, men and women should be included in a proportion equivalent to that observed for the condition studied. They also recommend that the impact of the gender on the results should be systematically studied.

Remuneration, freedom of choice, professional guinea pig.

The law of December 20, 1988 states that a participant in a clinical test without direct therapeutic benefit is not entitled to receive remuneration. Professionalism may be the strongest reason for participating. The law prohibits some participants from receiving an indemnity, not on the basis of healthy vs sick discrimination but when a situation of particular vulnerability or dependence has been established.

Double-blind placebo-controlled study of milnacipran in hospitalized patients with major depressive disorders.

Fifty-eight inpatients with a DSM-III diagnosis of major depressive disorder participated in a 5-week double-blind trial of milnacipran and placebo. Milnacipran was superior to placebo on all measures of depression. The first index of milnacipran superiority was the difference of dropouts due to treatment failure between milnacipran (10.3%) and placebo (55.2%). All patients were evaluated up to day 14. The improvement with milnacipran was statistically significant at day 14. Side effects were identical for milnacipran and placebo.

Prevention of migraine attacks through the use of dihydroergotamine.

A strictly controlled clinical trial on a group of 20 patients treated with a time-release preparation of dihydroergotamine compared with 20 on a placebo for the prevention of migraine attacks confirmed that dihydroergotamine was very effective and considered satisfactory by 65% of the patients treated.

[Evaluation of the efficacy of a venotonic capillary protector in the treatment of metrorrhagia due to IUD or micropill contraception]. / Appreciation de l'efficacite d'une association veinotonique protecteur capillaire comme traitement des metrorragies de la contraception par D.I.U. ou par micropilule.

PIP: Results are presented of a double blind trial of a venotonic capillary protector for treatment of metrorrhagia due to IUD or progestin micropill contraception. 20 randomly selected patients each with Gravigarde IUDs or using the low-dose oral contraceptive (OC) Milligynon containing norethindrone acetate received the venotonic while 20 others using each method received a placebo. The venotonic and placebo were to be taken in 4 daily capsules during 3 20-day treatment periods interrupted by the menstrual periods. Assessment criteria for the drug included subjective reports of improvement and objective reports of the number of days of bleeding intermenstrually, duration of bleeding, and number of sanitary napkins needed. The 2 groups of IUD users and the 2 groups of OC users were comparable in age, weight, and height. The duration of use of the IUD averaged about 7 months in both study and control groups. The pretreatment duration of intermenstrual bleeding averaged 8.5 days in the IUD treatment group, 6.8 in the IUD placebo group, 7.5 in the OC treatment group, and 6.6 in the OC placebo group. In all groups about 3 sanitary napkins were required for each episode. After 3 treatment cycles, 70% of patients in the 2 treatment groups but only 10% in the placebo groups reported that discomfort due to bleeding was absent or slight. Both treatment groups experienced highly significant reductions in the duration of intermenstrual bleeding, but the frequency of bleeding was very significantly lowered only after 3 treatment cycles. Tolerance of treatment was good or very good throughout the study for both the treatment and placebo groups.^ieng